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1.  Prospective multi-center trial utilizing electronic brachytherapy for the treatment of endometrial cancer 
Background
A modified form of high dose rate (HDR) brachytherapy has been developed called Axxent Electronic Brachytherapy (EBT). EBT uses a kilovolt X-ray source and does not require treatment in a shielded vault or a HDR afterloader unit. A multi-center clinical study was carried out to evaluate the success of treatment delivery, safety and toxicity of EBT in patients with endometrial cancer.
Methods
A total of 15 patients with stage I or II endometrial cancer were enrolled at 5 sites. Patients were treated with vaginal EBT alone or in combination with external beam radiation.
Results
The prescribed doses of EBT were successfully delivered in all 15 patients. From the first fraction through 3 months follow-up, there were 4 CTC Grade 1 adverse events and 2 CTC Grade II adverse events reported that were EBT related. The mild events reported were dysuria, vaginal dryness, mucosal atrophy, and rectal bleeding. The moderate treatment related adverse events included dysuria, and vaginal pain. No Grade III or IV adverse events were reported. The EBT system performed well and was associated with limited acute toxicities.
Conclusions
EBT shows acute results similar to HDR brachytherapy. Additional research is needed to further assess the clinical efficacy and safety of EBT in the treatment of endometrial cancer.
doi:10.1186/1748-717X-5-67
PMCID: PMC2914666  PMID: 20646289
2.  Use of electronic brachytherapy to deliver postsurgical adjuvant radiation therapy for endometrial cancer: a retrospective multicenter study 
OncoTargets and therapy  2010;3:197-203.
Background:
This retrospective, multicenter study evaluated the feasibility and safety of high-dose rate electronic brachytherapy (EBT) as a postsurgical adjuvant radiation therapy for endometrial cancer.
Methods:
Medical records were reviewed from 41 patients (age 40–89 years) with endometrial cancer (Federation of International Gynecology and Obstetrics stages IA–IIIC) treated at nine centers between April 2008 and October 2009. Treatment included intracavitary vaginal EBT alone (n = l6) at doses of 18.0–24.0 Gy in 3–4 fractions and EBT in combination with external beam radiation therapy (EBRT, n = 25) at a total radiation dose range of 40.0–80.4 Gy. Doses were prescribed to a depth of 5 mm from the applicator surface and to the upper third (n = 15) and the upper half (n = 26) of the vagina.
Results:
Median follow-up was 3.8 (range 0.5–12.0) months. All 41 patients received the intended dose of radiation as prescribed. Adverse events occurred in 13 of 41 patients and were mild to moderate (Grade 1–2), consisting primarily of vaginal mucositis, rectal mucosal irritation and discomfort, and temporary dysuria and diarrhea. There were no Grade 3 adverse events in the EBT-only treatment group. One patient, who was being treated with the combination of EBT and EBRT for recurrent endometrial cancer, had a Grade 3 adverse event. No recurrences have been reported to date.
Conclusion:
Electronic brachytherapy provides a feasible treatment option for postoperative adjuvant vaginal brachytherapy as sole radiation therapy and in combination with EBRT for primary endometrial cancer. Early and late toxicities were mild to moderate.
PMCID: PMC2962306  PMID: 21049086
endometrial cancer; electronic brachytherapy; radiation therapy
3.  Post-surgical treatment of early-stage breast cancer with electronic brachytherapy: an intersociety, multicenter brachytherapy trial 
OncoTargets and therapy  2010;3:211-218.
Introduction
Electronic brachytherapy (EBT) was developed to allow accelerated partial breast irradiation to be performed in a patient procedure room with minimal shielding. This observational, nonrandomized, multicenter study evaluated EBT as a post-surgical adjuvant radiation therapy for early stage breast cancer.
Methods
This study included women aged 50 years or more with invasive carcinoma or ductal carcinoma in situ, tumor size ≤3 cm, negative lymph node status, and negative surgical margins. The endpoints were skin and subcutaneous toxicities, efficacy outcomes, cosmetic outcomes, and device performance. In this interim report, 1-month, 6-month, and 1-year follow-up data are available on 68, 59, and 37 patients, respectively.
Results
The EBT device performed consistently, delivering the prescribed 34 Gy to all 69 patients (10 fractions/patient). Most adverse events were Grade 1 and included firmness, erythema, breast tenderness, hyperpigmentation, pruritis, field contracture, seroma, rash/desquamation, palpable mass, breast edema, hypopigmentation, telangiectasia, and blistering, which were anticipated. Breast infection occurred in two (2.9%) patients. No tumor recurrences were reported. Cosmetic outcomes were excellent or good in 83.9%–100% of evaluable patients at 1 month, 6 months, and 1 year.
Conclusion
This observational, nonrandomized, multicenter study demonstrates that this EBT device was reliable and well tolerated as an adjuvant radiation therapy for early stage breast cancer.
doi:10.2147/OTT.S14514
PMCID: PMC2994203  PMID: 21124748
radiation therapy; electronic brachytherapy; breast cancer
4.  The initial experience of electronic brachytherapy for the treatment of non-melanoma skin cancer 
Background
Millions of people are diagnosed with non-melanoma skin cancers (NMSC) worldwide each year. While surgical approaches are the standard treatment, some patients are appropriate candidates for radiation therapy for NMSC. High dose rate (HDR) brachytherapy using surface applicators has shown efficacy in the treatment of NMSC and shortens the radiation treatment schedule by using a condensed hypofractionated approach. An electronic brachytherapy (EBT) system permits treatment of NMSC without the use of a radioactive isotope.
Methods
Data were collected retrospectively from patients treated from July 2009 through March 2010. Pre-treatment biopsy was performed to confirm a malignant cutaneous diagnosis. A CT scan was performed to assess lesion depth for treatment planning, and an appropriate size of surface applicator was selected to provide an acceptable margin. An HDR EBT system delivered a dose of 40.0 Gy in eight fractions twice weekly with 48 hours between fractions, prescribed to a depth of 3-7 mm. Treatment feasibility, acute safety, efficacy outcomes, and cosmetic results were assessed.
Results
Thirty-seven patients (mean age 72.5 years) with 44 cutaneous malignancies were treated. Of 44 lesions treated, 39 (89%) were T1, 1 (2%) Tis, 1 (2%) T2, and 3 (7%) lesions were recurrent. Lesion locations included the nose for 16 lesions (36.4%), ear 5 (11%), scalp 5 (11%), face 14 (32%), and an extremity for 4 (9%). Median follow-up was 4.1 months. No severe toxicities occurred. Cosmesis ratings were good to excellent for 100% of the lesions at follow-up.
Conclusions
The early outcomes of EBT for the treatment of NMSC appear to show acceptable acute safety and favorable cosmetic outcomes. Using a hypofractionated approach, EBT provides a convenient treatment schedule.
doi:10.1186/1748-717X-5-87
PMCID: PMC2957390  PMID: 20875139
5.  Surgical perspectives from a prospective, nonrandomized, multicenter study of breast conserving surgery and adjuvant electronic brachytherapy for the treatment of breast cancer 
Background
Accelerated partial breast irradiation (APBI) may be used to deliver radiation to the tumor bed post-lumpectomy in eligible patients with breast cancer. Patient and tumor characteristics as well as the lumpectomy technique can influence patient eligibility for APBI. This report describes a lumpectomy procedure and examines patient, tumor, and surgical characteristics from a prospective, multicenter study of electronic brachytherapy.
Methods
The study enrolled 65 patients of age 45-84 years with ductal carcinoma or ductal carcinoma in situ, and 44 patients, who met the inclusion and exclusion criteria, were treated with APBI using the Axxent® electronic brachytherapy system following lumpectomy. The prescription dose was 34 Gy in 10 fractions over 5 days.
Results
The lumpectomy technique as described herein varied by site and patient characteristics. The balloon applicator was implanted by the surgeon (91%) or a radiation oncologist (9%) during or up to 61 days post-lumpectomy (mean 22 days). A lateral approach was most commonly used (59%) for insertion of the applicator followed by an incision site approach in 27% of cases, a medial approach in 5%, and an inferior approach in 7%. A trocar was used during applicator insertion in 27% of cases. Local anesthetic, sedation, both or neither were administered in 45%, 2%, 41% and 11% of cases, respectively, during applicator placement. The prescription dose was delivered in 42 of 44 treated patients.
Conclusions
Early stage breast cancer can be treated with breast conserving surgery and APBI using electronic brachytherapy. Treatment was well tolerated, and these early outcomes were similar to the early outcomes with iridium-based balloon brachytherapy.
doi:10.1186/1477-7819-9-30
PMCID: PMC3065420  PMID: 21385371
6.  Accelerated Partial Breast Irradiation (APBI): A review of available techniques 
Breast conservation therapy (BCT) is the procedure of choice for the management of the early stage breast cancer. However, its utilization has not been maximized because of logistics issues associated with the protracted treatment involved with the radiation treatment. Accelerated Partial Breast Irradiation (APBI) is an approach that treats only the lumpectomy bed plus a 1-2 cm margin, rather than the whole breast. Hence because of the small volume of irradiation a higher dose can be delivered in a shorter period of time. There has been growing interest for APBI and various approaches have been developed under phase I-III clinical studies; these include multicatheter interstitial brachytherapy, balloon catheter brachytherapy, conformal external beam radiation therapy and intra-operative radiation therapy (IORT). Balloon-based brachytherapy approaches include Mammosite, Axxent electronic brachytherapy and Contura, Hybrid brachytherapy devices include SAVI and ClearPath. This paper reviews the different techniques, identifying the weaknesses and strength of each approach and proposes a direction for future research and development. It is evident that APBI will play a role in the management of a selected group of early breast cancer. However, the relative role of the different techniques is yet to be clearly identified.
doi:10.1186/1748-717X-5-90
PMCID: PMC2958971  PMID: 20920346
7.  Dosimetry evaluation of SAVI-based HDR brachytherapy for partial breast irradiation 
Accelerated partial breast irradiation (APBI) with high dose rate (HDR) brachytherapy offers an excellent compact course of radiation due to its limited number of fractions for early-stage carcinoma of breast. One of the recent devices is SAVI (strut-adjusted volume implant), which has 6, 8 or 10 peripheral source channels with one center channel. Each channel can be differentially loaded. This paper focuses on the treatment planning, dosimetry and quality assurance aspects of HDR brachytherapy implant with GammaMed Plus HDR afterloader unit. The accelerated PBI balloon devices normally inflate above 35 cc range, and hence these balloon type devices cannot be accommodated in small lumpectomy cavity sizes. CT images were obtained and 3-D dosimetric plans were done with Brachyvision planning system. The 3-D treatment planning and dosimetric data were evaluated with planning target volume (PTV)_eval V90, V95, V150, V200 skin dose and minimum distance to skin. With the use of the SAVI 6-1 mini device, we were able to accomplish an excellent coverage — V90, V95, V150 and V200 to 98%, 95%, 37 cc (<50 cc volume) and 16 cc (<20 cc volume), respectively. Maximum skin dose was between 73% and 90%, much below the prescribed dose of 34 Gy. The minimum skin distance achieved was 5 to 11 mm. The volume that received 50% of the prescribed radiation dose was found to be lower with SAVI. The multi-channel SAVI-based implants reduced the maximum skin dose to markedly lower levels as compared to other modalities, simultaneously achieving best dose coverage to target volume. Differential-source dwell-loading allows modulation of the radiation dose distribution in symmetric or asymmetric opening of the catheter shapes and is also advantageous in cavities close to chest wall.
doi:10.4103/0971-6203.62127
PMCID: PMC2936181  PMID: 20927219
Accelerated partial breast irradiation; high dose rate; SAVI
8.  Evaluation of Gafchromic EBT2 film for the measurement of anisotropy function for high-dose-rate 192Ir brachytherapy source with respect to thermoluminescent dosimetry 
Aim
The aim of this work was to assess the suitability of the use of a Gafchromic EBT2 film for the measurement of anisotropy function for microSelectron HDR 192Ir (classic) source with a comparative dosimetry method using a Gafchromic EBT2 film and thermoluminescence dosimeters (TLDs).
Background
Sealed linear radiation sources are commonly used for high dose rate (HDR) brachytherapy treatments. Due to self-absorption and oblique filtration of radiation in the source capsule material, an inherent anisotropy is present in the dose distribution around the source which can be described by a measurable two-dimensional anisotropy function, F(r, θ).
Materials and methods
Measurements were carried out in a specially designed and locally fabricated PMMA phantom with provisions to accommodate miniature LiF TLD rods and EBT2 film dosimeters at identical radial distances with respect to the 192Ir source.
Results
The data of anisotropy function generated by the use of the Gafchromic EBT2 film method are in agreement with their TLD measured values within 4%. The produced data are also consistent with their experimental and Monte Carlo calculated results for this source available in the literature.
Conclusion
Gafchromic EBT2 film was found to be a feasible dosimeter in determining anisotropy in the dose distribution of 192Ir source. It offers high resolution and is a viable alternative to TLD dosimetry at discrete points. The method described in this paper is useful for comparing the performances of detectors and can be applied for other brachytherapy sources as well.
doi:10.1016/j.rpor.2010.11.003
PMCID: PMC3863320  PMID: 24376951
Anisotropy function; TL dosimetry; Gafchromic EBT2 film; HDR 192Ir source
9.  Monte Carlo simulations and radiation dosimetry measurements of peripherally applied HDR 192Ir breast brachytherapy D-shaped applicators 
Medical physics  2009;36(3):809-815.
Conformal dose coverage for accelerated partial breast irradiation or radiotherapy boost can be obtained with AccuBoost® D-shaped brachytherapy applicators using a flattened surface positioned near the patient. Three D-shaped applicators (D45/D53/D60) were dosimetrically characterized using Monte Carlo methods (MCNP5), air ionization chambers (Farmer and Markus), and radiochromic film (GafChromic EBT) in polystyrene and ICRU 44 breast tissue. HDR 192Ir source dwell times were either constant or optimized to improve skin dose uniformity. Scatter dose decreased as depth decreased. 10 mm beyond the applicator aperture, dose reductions of 90% and 51% were observed at depths of 0 and 30 mm, respectively. Similarly, planar dose uniformity improved as depth decreased and was also due to scatter and applicator geometry. Dose uniformity inside the applicator aperture was approximately 11% and 15% for all three applicators at the skin and 30 mm deep, respectively. Depth dose measurements in polystyrene using ion chamber and radiochromic film agreed with Monte Carlo results within 2%. Discrepancies between film and Monte Carlo dose profiles at 30 mm depth were within 1%.
doi:10.1118/1.3075818
PMCID: PMC2674240  PMID: 19378741
10.  Clinicopathologic Comparison of High-Dose-Rate Endorectal Brachytherapy versus Conventional Chemoradiotherapy in the Neoadjuvant Setting for Resectable Stages II and III Low Rectal Cancer 
Purpose. To assess for differences in clinical, radiologic, and pathologic outcomes between patients with stage II-III rectal adenocarcinoma treated neoadjuvantly with conventional external beam radiotherapy (3D conformal radiotherapy (3DRT) or intensity-modulated radiotherapy (IMRT)) versus high-dose-rate endorectal brachytherapy (EBT). Methods. Patients undergoing neoadjuvant EBT received 4 consecutive daily 6.5 Gy fractions without chemotherapy, while those undergoing 3DRT or IMRT received 28 daily 1.8 Gy fractions with concurrent 5-fluorouracil. Data was collected prospectively for 7 EBT patients and retrospectively for 25 historical 3DRT/IMRT controls. Results. Time to surgery was less for EBT compared to 3DRT and IMRT (P < 0.001). There was a trend towards higher rate of pathologic CR for EBT (P = 0.06). Rates of margin and lymph node positivity at resection were similar for all groups. Acute toxicity was less for EBT compared to 3DRT and IMRT (P = 0.025). Overall and progression-free survival were noninferior for EBT. On MRI, EBT achieved similar complete response rate and reduction in tumor volume as 3DRT and IMRT. Histopathologic comparison showed that EBT resulted in more localized treatment effects and fewer serosal adhesions. Conclusions. EBT offers several practical benefits over conventional radiotherapy techniques and appears to be at least as effective against low rectal cancer as measured by short-term outcomes.
doi:10.1155/2012/406568
PMCID: PMC3399366  PMID: 22830003
11.  Radiobiological characterization of post-lumpectomy focal brachytherapy with lipid nanoparticle-carried radionuclides 
Physics in medicine and biology  2011;56(3):703-719.
Post-operative radiotherapy has commonly been used for early stage breast cancer to treat residual disease. The primary objective of this work was to characterize, through dosimetric and radiobiological modeling, a novel focal brachytherapy technique which uses direct intracavitary infusion of β-emitting radionuclides (186Re/188Re) carried by lipid nanoparticles (liposomes). Absorbed dose calculations were performed for a spherical lumpectomy cavity with a uniformly injected activity distribution using a dose point kernel convolution technique. Radiobiological indices were used to relate predicted therapy outcome and normal tissue complication of this technique with equivalent external beam radiotherapy treatment regimens. Modeled stromal damage was used as a measure of the inhibition of the stimulatory effect on tumor growth driven by the wound healing response. A sample treatment plan delivering 50 Gy at a therapeutic range of 2.0 mm for 186Re-liposomes and 5.0 mm for 188Re-liposomes takes advantage of the dose delivery characteristics of the β-emissions, providing significant EUD (58.2 Gy and 72.5 Gy for 186Re and 188Re, respectively) with a minimal NTCP (0.046%) of the healthy ipsilateral breast. Modeling of kidney BED and ipsilateral breast NTCP showed that large injected activity concentrations of both radionuclides could be safely administered without significant complications.
PMCID: PMC3169207  PMID: 21299006
12.  Analysis of Fat Necrosis Following Adjuvant High-Dose-Rate Interstitial Brachytherapy for Early-Stage Breast Cancer 
Brachytherapy  2012;12(2):99-106.
Purpose
To report the incidence and potential predictors of fat necrosis in women with early-stage breast cancer treated with adjuvant high-dose-rate (HDR) multicatheter interstitial brachytherapy.
Methods and Materials
Between 2003 and 2010, 238 treated breasts in 236 women were treated with accelerated partial breast irradiation (APBI) using HDR interstitial brachytherapy. Selection criteria included patients with Tis-T2 tumors measuring ≤ 3 cm, without nodal involvement, who underwent breast-conserving surgery (BCS). 99% of treatments were to a total dose of 34 Gy. The presence and severity of fat necrosis was prospectively recorded during follow up. Cosmesis was qualitatively scored in all patients. Cosmesis was quantitatively measured via the percentage breast retraction assessment (pBRA) in 151 cases.
Results
Median follow-up was 56 months. The crude rate of fat necrosis was 17.6%. The rate of symptomatic fat necrosis was 10.1%. In univariate analysis acute breast infection and anthracycline-based chemotherapy, number of catheters, V100, V150, V200 and integrated reference air-kerma (IRAK) were significantly associated with fat necrosis. There was significant collinearity between the brachytherapy related factors, of these V150 was most predictive. In multivariate analysis only V150 was significantly associated with fat necrosis. At 3 years, patients with fat necrosis were more likely to have a fair/poor cosmetic outcome and a larger pBRA.
Conclusions
Mammary fat necrosis is a common adverse event after BCS and HDR interstitial brachytherapy. Fat necrosis is associated with worse qualitative and quantitative cosmetic outcomes. Minimizing exposure volumes such as V150 may decrease the incidence of fat necrosis and improve cosmesis.
doi:10.1016/j.brachy.2012.04.005
PMCID: PMC3929056  PMID: 22726878
Breast cancer; brachytherapy; fat necrosis; cosmesis; partial breast
13.  Radiation therapy for primary vaginal carcinoma 
Journal of Radiation Research  2013;54(5):931-937.
Brachytherapy plays a significant role in the management of cervical cancer, but the clinical significance of brachytherapy in the management of vaginal cancer remains to be defined. Thus, a single institutional experience in the treatment of primary invasive vaginal carcinoma was reviewed to define the role of brachytherapy. We retrospectively reviewed the charts of 36 patients with primary vaginal carcinoma who received definitive radiotherapy between 1992 and 2010. The treatment modalities included high-dose-rate intracavitary brachytherapy alone (HDR-ICBT; two patients), external beam radiation therapy alone (EBRT; 14 patients), a combination of EBRT and HDR-ICBT (10 patients), or high-dose-rate interstitial brachytherapy (HDR-ISBT; 10 patients). The median follow-up was 35.2 months. The 2-year local control rate (LCR), disease-free survival (DFS), and overall survival (OS) were 68.8%, 55.3% and 73.9%, respectively. The 2-year LCR for Stage I, II, III and IV was 100%, 87.5%, 51.5% and 0%, respectively (P = 0.007). In subgroup analysis consisting only of T2–T3 disease, the use of HDR-ISBT showed marginal significance for favorable 5-year LCR (88.9% vs 46.9%, P = 0.064). One patient each developed Grade 2 proctitis, Grade 2 cystitis, and a vaginal ulcer. We conclude that brachytherapy can play a central role in radiation therapy for primary vaginal cancer. Combining EBRT and HDR-ISBT for T2–T3 disease resulted in good local control.
doi:10.1093/jrr/rrt028
PMCID: PMC3766300  PMID: 23559599
primary vaginal cancer; radiation therapy; high-dose-rate brachytherapy; intracavitary brachytherapy; interstitial brachytherapy
14.  The dosimetric impact of vaginal balloon-packing on intracavitary high-dose-rate brachytherapy for gynecological cancer 
Purpose
We perform a clinical retrospective study to determine whether a vaginal balloon-packing system provides a dosimetric reduction to organs at risk (OARs) versus traditional gauze packing for gynecological high-dose-rate brachytherapy (HDR-BT). We also test various balloon filling materials for optimizing imaging quality.
Material and methods
Filling materials for balloon-packing were evaluated based on imaging quality with X-ray, computerized tomography, and magnetic resonance imaging modalities. We then retrospectively reviewed 45 HDR-BT plans of 18 patients performed with gauze packing and 39 plans of 16 patients performed with balloon-packing. Twelve patients received both gauze and balloon-packing. HDR-BT was delivered with an iridium-192 afterloader and a Fletcher-Suit-Declos-style T&O applicator. At each fraction, 3D imaging was obtained. The D2cc values of OARs were calculated, as well as ICRU-defined point doses.
Results
In the 84 HDR fractions reviewed, vaginal balloon-packing provides statistically equivalent doses to rectum, bladder, and sigmoid compared to gauze packing. On average balloon-packing produced average reductions of 3.3% and 6.9% in the rectal and sigmoid D2cc doses and an increase of 3.2% to the bladder D2cc dose (normalized to prescription dose), although none of these values were statistically significant for the twelve patients who received both gauze and balloon-packing (32 and 40 total fractions, respectively).
Conclusions
In the 84 HDR fractions analyzed, vaginal balloon-packing is as effective as gauze packing for dose sparing to the rectum, bladder, and sigmoid. A 1: 1 solution of saline and contrast for filling material enables easy contouring for image-guided HDR with minimal artefacts.
doi:10.5114/jcb.2013.34449
PMCID: PMC3635049  PMID: 23634151
brachytherapy; gynecological cancer; high-dose-rate brachytherapy; vaginal balloon packing
15.  Brachytherapy in the therapy of prostate cancer – an interesting choice 
Contemporary Oncology  2013;17(5):407-412.
Brachytherapy is a curative alternative to radical prostatectomy or external beam radiation [i.e. 3D conformal external beam radiation therapy (CRT), intensity-modulated radiation therapy (IMRT)] with comparable long-term survival and biochemical control and the most favorable toxicity. HDR brachytherapy (HDR-BT) in treatment of prostate cancer is most frequently used together with external beam radiation therapy (EBRT) as a boost (increasing the treatment dose precisely to the tumor). In the early stages of the disease (low, sometimes intermediate risk group), HDR-BT is more often used as monotherapy. There are no significant differences in treatment results (overall survival rate – OS, local recurrence rate – LC) between radical prostatectomy, EBRT and HDR-BT. Low-dose-rate brachytherapy (LDR-BT) is a radiation method that has been known for several years in treatment of localized prostate cancer. The LDR-BT is applied as a monotherapy and also used along with EBRT as a boost. It is used as a sole radical treatment modality, but not as a palliative treatment. The use of brachytherapy as monotherapy in treatment of prostate cancer enables many patients to keep their sexual functions in order and causes a lower rate of urinary incontinence. Due to progress in medical and technical knowledge in brachytherapy (“real-time” computer planning systems, new radioisotopes and remote afterloading systems), it has been possible to make treatment time significantly shorter in comparison with other methods. This also enables better protection of healthy organs in the pelvis. The aim of this publication is to describe both brachytherapy methods.
doi:10.5114/wo.2013.38557
PMCID: PMC3934024  PMID: 24596528
HDR brachytherapy; LDR brachytherapy; prostate cancer; seeds
16.  Partial breast irradiation techniques in early breast cancer 
Whole breast irradiation represents an integral part of combined breast-conserving treatment of early breast cancer. A new concept includes replacing traditionally fractionated whole breast postoperative radiotherapy by accelerated partial breast irradiation. The latter involves a variety of techniques and may be applied intraoperatively or shortly after the surgery. The intraoperative techniques include photon or electron external beam irradiation and interstitial high dose rate (HDR) brachytherapy, whereas the postoperative techniques comprise interstitial brachytherapy, be it HDR, pulse dose rate (PDR) or low dose rate (LDR), intracavitary brachytherapy and external beam radiotherapy using electrons, photons or protons. This article presents accelerated partial breast irradiation techniques, ongoing phase III trials evaluating their value and recommendations for clinical practice.
doi:10.1016/j.rpor.2011.08.003
PMCID: PMC3863308  PMID: 24376983
Breast cancer; Adjuvant radiotherapy; Whole breast irradiation; Accelerated partial breast irradiation
17.  Biological effective doses in the intracavitary high dose rate brachytherapy of cervical cancer 
Purpose
The aim of this study is to evaluate the decrease of biological equivalent dose and its correlation with local/loco-regional control of tumour in the treatment of cervical cancer when the strength of the Ir-192 high dose rate (HDR) brachytherapy (BT) source is reduced to single, double and triple half life in relation to original strength of 10 Ci (∼ 4.081 cGy x m2 x h−1).
Material and methods
A retrospective study was carried out on 52 cervical cancer patients with stage II and III treated with fractionated HDR-BT following external beam radiation therapy (EBRT). International Commission on Radiation Units and Measurement (ICRU) points were defined according to ICRU Report 38, using two orthogonal radiograph images taken by Simulator (Simulix HQ). Biologically effective dose (BED) was calculated at point A for different Ir-192 source strength and its possible correlation with local/loco-regional tumour control was discussed.
Result
The increase of treatment time per fraction of dose due to the fall of dose rate especially in HDR-BT of cervical cancer results in reduction in BED of 2.59%, 7.02% and 13.68% with single, double and triple half life reduction of source strength, respectively. The probabilities of disease recurrence (local/loco-regional) within 26 months are expected as 0.12, 0.12, 0.16, 0.39 and 0.80 for source strength of 4.081, 2.041, 1.020, 0.510 and 0.347 cGy x m2 x h−1, respectively. The percentages of dose increase required to maintain the same BED with respect to initial BED were estimated as 1.71, 5.00, 11.00 and 15.86 for the dose rate of 24.7, 12.4, 6.2 and 4.2 Gy/hr at point A, respectively.
Conclusions
This retrospective study of cervical cancer patients treated with HDR-BT at different Ir-192 source strength shows reduction in disease free survival according to the increase in treatment time duration per fraction. The probable result could be associated with the decrease of biological equivalent dose to point A. Clinical end point of this study is more significant from double half life reduction of original source strength.
doi:10.5114/jcb.2011.26469
PMCID: PMC3551365  PMID: 23346127
HDR brachytherapy; cervical cancer; biological effective dose; dose rate
18.  Brachytherapy for cervix cancer: low-dose rate or high-dose rate brachytherapy – a meta-analysis of clinical trials 
Background
The literature supporting high-dose rate brachytherapy (HDR) in the treatment of cervical carcinoma derives primarily from retrospective series. However, controversy still persists regarding the efficacy and safety of HDR brachytherapy compared to low-dose rate (LDR) brachytherapy, in particular, due to inadequate tumor coverage for stage III patients. Whether LDR or HDR brachytherapy produces better results for these patients in terms of survival rate, local control rate and the treatment complications remain controversial.
Methods
A meta-analysis of RCT was performed comparing LDR to HDR brachytherapy for cervix cancer treated for radiotherapy alone. The MEDLINE, EMBASE, CANCERLIT and Cochrane Library databases, as well as abstracts published in the annual proceedings were systematically searched. We assessed methodological quality for each outcome by grading the quality of evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. We used "recommend" for strong recommendations, and "suggest" for weak recommendations.
Results
Pooled results from five randomized trials (2,065 patients) of HDR brachytherapy in cervix cancer showed no significant increase of mortality (p = 0.52), local recurrence (p = 0.68), or late complications (rectal; p = 0.7, bladder; p = 0.95 or small intestine; p = 0.06) rates as compared to LDR brachytherapy. In the subgroup analysis no difference was observed for overall mortality and local recurrence in patients with clinical stages I, II and III. The quality of evidence was low for mortality and local recurrence in patients with clinical stage I, and moderate for other clinical stages.
Conclusion
Our meta-analysis shows that there are no differences between HDR and LDR for overall survival, local recurrence and late complications for clinical stages I, II and III. By means of the GRADE system, we recommend the use of HDR for all clinical stages of cervix cancer.
doi:10.1186/1756-9966-28-47
PMCID: PMC2673206  PMID: 19344527
19.  Dosimetry and toxicity outcomes in postoperative high-dose-rate intracavitary brachytherapy for endometrial carcinoma 
Purpose
The optimal dosimetric parameters and planning techniques for high-dose-rate vaginal brachytherapy (HDR-VB) are unclear. Our aim was to evaluate the utility of bladder and rectal dosimetry for patients receiving HDR-VB for postoperative treatment of endometrial carcinoma.
Material and methods
Patients with endometrial cancer who underwent postoperative HDR-VB from January 1, 2004 through December 31, 2010 were included. All patients underwent primary surgery consisting of total hysterectomy and bilateral salpingo-oophrectomy (TH-BSO) with or without lymph node dissection and were treated with HDR-VB without pelvic external beam radiotherapy (EBRT) or chemotherapy. Demographic, pathologic, dosimetric and clinical data were collected.
Results
One hundred patients were identified with the majority of patients receiving HDR-VB in 700 cGy × 3 fractions (45%) or 550 cGy x 4 fractions (53%). No plan was altered based on bladder dosimetry at the time of planning. The rate of acute urinary reactions (< 90 days from beginning of RT) grades 1 and 2 were 14% and 2%, respectively. The rate of late urinary reactions (> 90 days after RT) grades 1 and 2 were 7% and 3%, respectively. Dose to the bladder point did not correlate with urinary toxicity. No rectal toxicity was reported by patients receiving HDR-VB.
Conclusions
In the setting of HDR-VB without EBRT, the measured dose to the bladder point does not predict urinary toxicity and is very unlikely to indicate the need to change the treatment plan. The treatment of endometrial carcinoma utilizing HDR-VB alone is associated with very low rates of high-grade acute or late bladder toxicity.
doi:10.5114/jcb.2012.30679
PMCID: PMC3551376  PMID: 23346142
endometrial cancer; high-dose-rate; brachytherapy
20.  A Phase II Trial of Brachytherapy Alone Following Lumpectomy for Select Breast Cancer: tumor control and survival outcomes of RTOG 95-17 
Purpose:
RTOG 95-17 is a prospective Phase II cooperative group trial of APBI alone using multicatheter brachytherapy following lumpectomy in select early stage breast cancers. Tumor control and survival outcomes are reported.
Materials and Methods:
Eligibility criteria included stage I/II breast carcinoma confirmed to be <3cm, unifocal, invasive non-lobular histology with 0-3 positive axillary nodes without extracapsular extension. APBI treatment was delivered with either Low Dose Rate (LDR) (45 Gy in 3.5-5 days) or High Dose Rate (HDR) (34 Gy in 10 BID fractions over 5 days). Endpoints evaluated included in-breast control, regional control, mastectomy-free rate, mastectomy-free survival, disease-free survival and overall survival. The study was designed to analyze the HDR and LDR groups separately and without comparison.
Results:
Between 1997 and 2000, 100 patients were accrued and 99 were eligible; 66 treated with HDR and 33 treated with LDR. Eighty seven patients had T1 lesions and 12 had T2 lesions. Seventy nine were pathologically N0 and 20 were N1. Median follow-up in the HDR group is 6.14 years with the 5-year estimates of in-breast, regional and contralateral failure rates of 3%, 5% and 2%, respectively. The LDR group experienced similar results with a median follow-up of 6.22 years. The 5-year estimates of in-breast, regional and contralateral failure rates of 6%, 0% and 6%, respectively.
Conclusion:
Patients treated with multicatheter partial breast brachytherapy on this trial experienced excellent in-breast control rates and overall outcome that compare to reports from APBI studies with similar extended follow-up.
doi:10.1016/j.ijrobp.2007.12.056
PMCID: PMC2604132  PMID: 18294778
Brachytherapy; breast cancer; breast cancer trials; radiation therapy for breast cancer; accelerated partial breast irradiation
21.  Imaging of osteo-odonto-keratoprosthesis by electron beam tomography 
Aim: To describe the experience of using electron beam tomography (EBT) in imaging of osteo-odonto-keratoprosthesis (OOKP) to identify early bone and dentine loss which may threaten the viability of the eye.
Methods: Seven patients with an OOKP in one eye underwent EBT. The OOKP lamina dimensions were measured on EBT and compared to the manual measurements at the time of surgery.
Results: There was a high degree of resolution of the OOKP lamina noted with EBT. In particular, it identified three patients with a marked degree of thinning of the lamina edges. Two of these patients had OOKP that were allografts. The mean time from surgery to examination was 3.6 years (range 1.2–5 years) while the mean age of the patients was 56 years (range 31–79 years).
Conclusions: It is important to monitor regularly the dimensions and stability of the OOKP lamina as it will help detect cases that are at risk of extrusion of the optical cylinder and consequent endophthalmitis. Prophylactic measures can then be taken to prevent such serious complications from occurring. In this series, the authors found EBT to have excellent resolution and speed and they would support regular scanning of the OOKP lamina in all patients.
doi:10.1136/bjo.2004.061424
PMCID: PMC1772762  PMID: 16024842
osteo-odonto-keratoprosthesis; electron beam tomography
22.  Association Between Treatment With Brachytherapy vs Whole-Breast Irradiation and Subsequent Mastectomy, Complications, and Survival Among Older Women With Invasive Breast Cancer 
Jama  2012;307(17):1827-1837.
Context
Brachytherapy is a radiation treatment that uses an implanted radioactive source. In recent years, use of breast brachytherapy after lumpectomy for early breast cancer has increased substantially despite a lack of randomized trial data comparing its effectiveness with standard whole-breast irradiation (WBI). Because results of long-term randomized trials will not be reported for years, detailed analysis of clinical outcomes in a nonrandomized setting is warranted.
Objective
To compare the likelihood of breast preservation, complications, and survival for brachytherapy vs WBI among a nationwide cohort of older women with breast cancer with fee-for-service Medicare.
Design
Retrospective population-based cohort study of 92 735 women aged 67 years or older with incident invasive breast cancer, diagnosed between 2003 and 2007 and followed up through 2008. After lumpectomy 6952 patients were treated with brachytherapy vs 85 783 with WBI.
Main Outcome Measures
Cumulative incidence and adjusted risk of subsequent mastectomy (an indicator of failure to preserve the breast) and death were compared using the log-rank test and proportional hazards models. Odds of postoperative infectious and noninfectious complications within 1 year were compared using the χ2 test and logistic models. Cumulative incidences of long-term complications were compared using the log-rank test.
Results
Five-year incidence of subsequent mastectomy was higher in women treated with brachytherapy (3.95%; 95% CI, 3.19%–4.88%) vs WBI (2.18%; 95% CI, 2.04%–2.33%; P<.001) and persisted after multivariate adjustment (hazard ratio [HR], 2.19; 95% CI, 1.84–2.61, P<.001). Brachytherapy was associated with more frequentinfectious (16.20%; 95% CI, 15.34%–17.08% vs 10.33%; 95% CI, 10.13%–10.53%; P<.001; adjusted odds ratio [OR], 1.76; 1.64–1.88) and noninfectious (16.25%; 95% CI, 15.39%–17.14% vs 9.00%; 95% CI, 8.81%–9.19%; P<.001; adjusted OR, 2.03; 95% CI, 1.89–2.17) postoperative complications; and higher 5-year incidence of breast pain (14.55%, 95% CI, 13.39%–15.80% vs 11.92%; 95% CI, 11.63%–12.21%), fat necrosis (8.26%; 95% CI, 7.27–9.38 vs 4.05%; 95% CI, 3.87%–4.24%), and rib fracture (4.53%; 95% CI, 3.63%–5.64% vs 3.62%; 95% CI, 3.44%–3.82%; P≤.01 for all). Five-year overall survival was 87.66% (95% CI, 85.94%–89.18%) in patients treated with brachytherapy vs 87.04% (95% CI, 86.69%–87.39%) in patients treated with WBI (adjusted HR, 0.94; 95% CI, 0.84–1.05; P=.26).
Conclusion
In a cohort of older women with breast cancer, treatment with brachytherapy compared with WBI was associated with worse long-term breast preservation and increased complications but no difference in survival.
doi:10.1001/jama.2012.3481
PMCID: PMC3397792  PMID: 22550197
23.  A Novel Low Dose Fractionation Regimen for Adjuvant Vaginal Brachytherapy in Early Stage Endometrial Cancer 
Gynecologic oncology  2012;127(2):351-355.
Purpose
To evaluate local control, survival and toxicity in patients with early-stage endometrioid adenocarcinoma of the uterus treated with adjuvant high-dose-rate (HDR) vaginal brachytherapy (VB) alone using a novel low dose regimen
Methods
We reviewed records of 414 patients with stage IA to stage II endometrial adenocarcinoma treated with VB alone from 2005 to 2011. Of these, 157 patients with endometrioid histology received 24 Gy in 6 fractions of HDR vaginal cylinder brachytherapy and constitute the study population. Dose was prescribed at the cylinder surface and delivered twice weekly in the post-operative setting. Local control and survival rates were calculated by the Kaplan-Meier method.
Results
All 157 patients completed the prescribed course of VB. Median follow-up time was 22.8 months (range, 1.5–76.5). Two patients developed vaginal recurrence, one in the periurethral region below the field and one in the fornix after treatment with a 2.5-cm cylinder. Three patients developed regional recurrence in the para-aortic region. Two patients developed distant metastasis (lung and carcinomatosis). The 2-year rate of vaginal control was 98.6%, locoregional control was 97.9% and disease-free survival was 96.8%. The 2-year overall survival rate was 98.7%. No Grade 2 or higher vaginal, gastrointestinal, genitourinary or skin long-term toxicity was reported for any patient.
Conclusion
Vaginal brachytherapy alone in early-stage endometrial cancer provides excellent results in terms of locoregional control and disease-free survival. The fractionation scheme of 24 Gy in 6 fractions prescribed to the cylinder surface was well-tolerated with minimal late toxicity.
doi:10.1016/j.ygyno.2012.07.111
PMCID: PMC3548566  PMID: 22850411
Endometrial cancer; vaginal brachytherapy; high-dose-rate
24.  High Dose Rate Brachytherapy in the Treatment of cervical cancer: preliminary experience with cobalt 60 Radionuclide source—A Prospective Study 
Iridium-192 is widely used for high-dose rate brachytherapy. Co-60 source with similar geometric and dosimetric properties are now available. It has a longer half life but higher energy than Iridium-192. If Co-60 source can produce similar results, it will be more economical for low resource settings.
Objective:
To evaluate the acute gastrointestinal and genitourinary toxicity associated with Co-60 source in the brachytherapy of cervical cancer.
Methods:
Seventy patients with cervical cancer received 45 Gy in 22 fractions of pelvic external beam radiotherapy and 19.5 Gy in 3 fractions of HDR with Co-60 source using tandem and ring applicators with 6 courses of cisplatin 50 mg/m2 and 5 fluorouracil 1000 mg/m2 every 3 weeks Toxicity was scored using NCI-CTC version 4.0.
Results:
The median total BED (Gy10) for tumor was 86.2 (84.4–88.8) while that for rectum (BED Gy3) was 124.4 (120–133). Two patients (3%) had grade 3 gastrointestinal toxicity while all others had ≤grade 2 toxicity and this is comparable with previous results.
Conclusion:
Co-60 as HDR brachytherapy source is tolerable and is economical for low resource settings.
PMCID: PMC2934612  PMID: 20838638
HDR brachytherapy; Co-60 source; cervical cancer; acute toxicity
25.  Dosimetric impact of point A definition on high-dose-rate brachytherapy for cervical cancer: evaluations on conventional point A and MRI-guided, conformal plans 
Purpose
To investigate the dosimetric impact of point A definitions on both conventional point A plans and MRI-guided conformal high-dose-rate (HDR) brachytherapy plans.
Material and methods
Fifty-five HDR plans of 36 patients with FIGO stage I to IV cervical cancer were retrospectively studied; these included 30 conventional treatments and 25 conformal plans. Two different point A definitions were explored: the revised Manchester point A and the new point A as recommended by the American Brachytherapy Society. Conventional plans were produced by varying only the point A definition and the normalized isodose lines. Conformal plans were retrospectively generated per GEC-ESTRO recommendations based upon 3.0 Tesla MRI data.
Results
Small yet significant variations were found in point A locations (mean: 0.5 cm, maximum: 2.1 cm, p < 0.001). The use of a new point A caused minimal dose variation for both conventional and conformal plans. Conventional plans normalized to the new point A generated up to 12% (avg. 1-3%) higher overall dose in terms of higher total reference air kerma than plans normalized to other points. Dosimetric changes due to point A definitions were up to 11-12% (avg. less than 2%) on target volumes or organs-at-risk.
Conclusions
For both conventional and conformal plans, the new point A definition leads to smaller variations caused during implant and/or differences in patient anatomy. Using the new point A is expected to produce more consistent brachytherapy plans and improve outcome analysis.
doi:10.5114/jcb.2012.32559
PMCID: PMC3561607  PMID: 23378854
brachytherapy; cervical cancer; high-dose-rate brachytherapy; MRI-guided; point A

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